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101.
Franziska Berger Helene Geddert Gerhard Faller Martin Werner Arno Dimmler 《Pathology, research and practice》2014
Purpose
Increasing evidence indicates that TGFbeta- and EGFR-signaling is involved in the pathogenesis of keratoacanthoma (KA) and squamous cell carcinoma (SCC) of the skin. We analyzed the expression pattern of TGFbeta-signaling components and screened for mutations in tgfbetaR1, egfr, kras and braf in KAs and SCCs.Methods
Immunohistochemical analysis of TGFbeta1, TGFbetaR1, TGFbetaR2 and phospho-SMAD2/3 was performed on skin tumors (29 KAs, 30 well and 31 moderately differentiated SCCs). Mutation screening in hotspot regions of tgfbetaR1, egfr, kras and braf was performed through pyrosequencing of tumor DNA.Findings
Expression of TGFbeta1, TGFbetaR1 and p-SMAD2/3 was increased in tumors as compared to surrounding skin. In KAs characteristic strong discontinuous membranous TGFbetaR1 expression pattern frequently associated with kras mutation was noted. SCCs showed continuous TGFbetaR1 expression, stronger p-SMAD2/3 expression and less frequent kras mutations. In tumors at sun-exposed sites stronger TGFbetaR1 expression was noted. One SCC showed tgfbetaR1 mutation, but no other mutations were found.Conclusion
Although tgfbetaR1 germline mutations cause inherited KAs and our finding of strong discontinuous membranous expression in KAs suggests accumulation of functionally altered protein, we found no tgfbetaR1 mutations or influence on TGFbeta-signaling, but frequent kras mutations in this subgroup of KAs. Characteristic TGFbetaR1 expression pattern in KA can facilitate histopathologic distinction from SCC. 相似文献102.
Andreas Marx Lena Koopmann Doris Hoflmayer Franziska Büscheck Claudia Hube-Magg Stefan Steurer Till Eichenauer Till S.Clauditz Waldemar Wilczak Ronald Simon Guido Sauter Jakob R.Izbicki Hartwig Huland Hans Heinzer Markus Graefen Alexander Haese Thorsten Schlomm Christian Bernreuther Patrick Lebok Sarah Bonk 《癌症生物学与医学(英文版)》2021,(1):245-255
Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa. 相似文献
103.
Therese Muzeniek Thejanee Perera Sahan Siriwardana Dilara Bas Fatimanur Kaplan Mizgin
ruc Beate Becker-Ziaja Inoka Perera Jagathpriya Weerasena Shiroma Handunnetti Franziska Schwarz Gayani Premawansa Sunil Premawansa Wipula Yapa Andreas Nitsche Claudia Kohl 《Viruses》2022,14(2)
Coronaviruses (CoV) are divided into the genera α-CoVs, β-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and β-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the β-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and β-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and β-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus. 相似文献
104.
Franziska C. Adam Jakub Szybinski Jrg P. Halter Nathan Cantoni Friedel Wenzel Katharina Leonards Sime Brkic Jakob R. Passweg Ivo Touw Julia E. Maxson Sara C. Meyer 《Current oncology (Toronto, Ont.)》2022,29(2):805
Chronic neutrophilic leukemia (CNL) relates to mutational CSF3R activation with membrane proximal CSF3R mutations such as T618I as driver mutations, but the significance of truncating mutations is not clarified. In CNL, concomitant mutations promote disease progression, but insight into longitudinal acquisition is incomplete. In this study, we investigated the role of co-occurring germline and somatic CSF3R mutations in CNL, and assessed the impact of clonal evolution on transformation to acute leukemia. We employed sequential next generation sequencing and SNP array karyotyping to assess clonal evolution in CNL of early manifestation age based on a 33-year-old patient. Germline vs. somatic mutations were differentiated using a sample from the hair follicle. To investigate a potential predisposition for CNL development and progression by germline CSF3R-W791*, allelic localizations were evaluated. We detected a somatic CSF3R-T618I mutation at 46% variant allele frequency (VAF) at the time of CNL diagnosis, which co-occurred with a CSF3R-W791* truncation at 50% VAF in the germline. Evaluation of allelic localization revealed CSF3R-T618I and W791* on the same allele. A concomitant ASXL1 mutation at 39% VAF increased to 48% VAF upon transformation to mixed phenotype acute leukemia (MPAL), which has both myeloid and lymphoid features. Clonal evolution further involved expansion of the CSF3R double-mutant clone to 90% VAF via copy neutral loss of heterozygosity on chromosome 1p and the emergence of a RUNX1 mutant subclone. Allogeneic transplantation induced complete remission. This study highlights that CNL not only transforms to AML but also to MPAL. The molecular evolution is especially interesting with a CSF3R-W791* mutation in the germline and acquisition of CSF3R-T618I on the same allele compatible with increased susceptibility for mutation acquisition facilitating RUNX1-related clonal transformation. 相似文献
105.
Till Joscha Demal Lennart Bax Jens Brickwedel Tilo Klbel Eik Vettorazzi Franziska Sitzmann Hermann Reichenspurner Christian Detter 《Interactive Cardiovascular and Thoracic Surgery》2021,33(1):85
Open in a separate windowOBJECTIVESThe goal of this study was to determine the outcome of patients undergoing an elective frozen elephant trunk (FET) procedure as a redo operation following previous cardiac surgery.METHODSOne hundred and eighteen consecutive patients underwent FET procedures between October 2010 and October 2019 at our centre. Patients were registered in a dedicated database and analysed retrospectively. Clinical and follow-up characteristics were compared between patients undergoing a FET operation as a primary (primary group) or a redo procedure (redo group) using logistic regression and Cox regression analysis. Emergency procedures (n = 33) were excluded from the analysis.RESULTSA total of 36.5% (n = 31) of the FET procedures were redo operations (redo group) and 63.5% (n = 54) of the patients underwent primary surgery (primary group). There was no significant difference in the 30-day mortality [primary group: 7.4%; redo group: 3.2%; 95% confidence interval (CI) (0.19–35.29); P = 0.63] and the 3-year mortality [primary group: 22.2%; redo group: 16.7%; 95% CI (0.23–3.23); P = 0.72] between redo and primary cases. Furthermore, the adjusted statistical analysis did not reveal significant differences between the groups in the occurrence of transient or permanent neurological deficit, paraplegia, acute renal failure and resternotomy. The redo group showed a higher rate of recurrent nerve palsy, which did not reach statistical significance [primary group: 3.7% (n = 2); redo group: 19.4% (n = 6); P = 0.091].CONCLUSIONSElective FET procedures as redo operations performed by a dedicated aortic team following previous cardiac surgery demonstrate an adequate safety profile. 相似文献
106.
Victoria A. Malik Franziska Zajicek Laura A. Mittmann Johannes Klaus Sandra Unterseer Sandeep Rajkumar Benno Pütz Jan M. Deussing Inga D. Neumann Rainer Rupprecht Barbara Di Benedetto 《Journal of neuroscience research》2020,98(7):1433-1456
Perivascular astrocyte processes (PAP) surround cerebral endothelial cells (ECs) and modulate the strengthening of tight junctions to influence blood–brain barrier (BBB) permeability. Morphologically altered astrocytes may affect barrier properties and trigger the onset of brain pathologies. However, astrocyte-dependent mediators of these events remain poorly studied. Here, we show a pharmacologically driven elevated expression and release of growth/differentiation factor 15 (GDF15) in rat primary astrocytes and cerebral PAP. GDF15 has been shown to possess trophic properties for motor neurons, prompting us to hypothesize similar effects on astrocytes. Indeed, its increased expression and release occurred simultaneously to morphological changes of astrocytes in vitro and PAP, suggesting modulatory effects of GDF15 on these cells, but also neighboring EC. Administration of recombinant GDF15 was sufficient to promote astrocyte remodeling and enhance barrier properties between ECs in vitro, whereas its pharmacogenetic abrogation prevented these effects. We validated our findings in male high anxiety-related behavior rats, an animal model of depressive-like behavior, with shrunk PAP associated with reduced expression of the junctional protein claudin-5, which were both restored by a pharmacologically induced increase in GDF15 expression. Thus, we identified GDF15 as an astrocyte-derived trigger of astrocyte process remodeling linked to enhanced tight junction strengthening at the BBB. 相似文献
107.
Calwing Liao BSc Faezeh Sarayloo MSc Daniel Rochefort MSc Gabrielle Houle BSc Fulya Akçimen MSc Qin He PhD Alexandre D. Laporte MSc Dan Spiegelman MSc Werner Poewe MD Daniela Berg MD Stefanie Müller PhD Franziska Hopfner MD PhD Günther Deuschl MD PhD Gregor Kuhlenbäeumer MD PhD Alex Rajput MD Patrick A. Dion PhD Guy A. Rouleau MD PhD 《Movement disorders》2020,35(7):1153-1162
108.
109.
110.
Matthias Pfisterer Hans Peter Brunner-La Rocca Peter T Buser Peter Rickenbacher Patrick Hunziker Christian Mueller Raban Jeger Franziska Bader Stefan Osswald Christoph Kaiser 《Journal of the American College of Cardiology》2006,48(12):2584-2591
OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivit?ts Trial). The primary focus of this observation was cardiac death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis. 相似文献